The Hungarian biochemist and US immunologist whose scientific breakthroughs enabled the development of mRNA vaccines against COVID-19 have been rewarded as joint winners of the $1.6 million Nobel prize in physiology/medicine.
Dr Katalin Karikó (PhD) and Dr Drew Weissman met by chance while photocopying research papers in the late 1990s and spent decades publishing papers on mRNA in technical science journals.
Papers such as ‘The impact of nucleoside modification and the evolutionary origin of RNA’ and ‘Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation’ did not receive widespread attention at the time.
Yet they ultimately led to more than two billion mRNA vaccines administered globally during the COVID-19 pandemic.
And importantly, it is hoped their work will be used for the development of other vaccines as well as non-vaccine therapies, including cancer treatments.
Dr Karikó said she was an advocate for the potential of mRNA since the 1980s, but a lack of research funding prompted a move from Hungary to the US along with her husband and their young daughter.
At the time, the Hungarian Government only allowed people to take $100 out of the country, so the family sewed $1700 they received from selling their car into their daughter’s teddy bear, Dr Karikó told The Guardian.
She took on a postdoctoral position at Temple University, and in 1989, started as a research assistant professor at the University of Pennsylvania.
Here she met Dr Weissman.
“I told him, ‘I am an RNA scientist — I can make anything with mRNA,’” Dr. Karikó recalled.
Dr Weissman’s interest was in developing a vaccine for HIV.
“I said, ‘Yeah, yeah, I can do it,’” Dr Karikó said.
However, their work was stymied when lab-made mRNA caused fatal inflammation in mice.
They investigated the chemical modifications in RNA created by cells — called post-transcriptional modifications — and identified pseudouridine as the key ingredient for viable mRNA therapies.
Another breakthrough was a new vaccine delivery platform, a lipid nanoparticle that protected the mRNA until it reached its destination.
Yet mRNA technology was still dismissed as vaccine development dead-end.
“We talked to pharmaceutical companies and venture capitalists; no-one cared,” Dr Weissman told The New York Times.
“We were screaming a lot, but no-one would listen.”
Eventually, both Moderna and BioNTech took interest and launched clinical trials of an mRNA flu vaccine.
When the COVID-19 pandemic broke out, the companies could switch to making mRNA vaccines against the virus within days.
Pfizer announced that its Comirnaty vaccine appeared to protect against death from COVID-19 in a press release on 8 November 2020.
Dr Karikó said she celebrated the news by eating a box of chocolate-coated peanuts, while Dr Weissmann splurged by ordering takeaway food “with wine” for his family’s dinner that night.
Without the drive of a global pandemic, the next steps for mRNA seem to have returned to the typical scientific timescale.
The mRNA influenza vaccines promised by Moderna and Pfizer are still being trialled, and Dr Weissman’s dream for an mRNA-based HIV vaccine is yet to come true.
Both Dr Karikó and Dr Weissman are continuing their research.
They still hold positions at the University of Pennsylvania, while Dr Karikó is also senior vice-president at BioNTech.
Announcing the award for Dr Karikó and Dr Weissman, the Nobel prize committee said mRNA vaccines “saved millions of lives and prevented severe disease in many more”.
“Through their fundamental discoveries of the importance of base modifications in mRNA, this year’s Nobel laureates critically contributed to this transformative development during one of the biggest health crises of our time.”